Evolutionary Dynamics of Accelerated Antiviral Resistance Development in Hypermutator Herpesvirus.
| Autor: | Höfler T; Institut für Virologie, Fachbereich Veterinärmedizin, Freie Universität Berlin, Berlin, Germany., Nascimento MM; Institut für Virologie, Fachbereich Veterinärmedizin, Freie Universität Berlin, Berlin, Germany., Zeitlow M; Institut für Virologie, Fachbereich Veterinärmedizin, Freie Universität Berlin, Berlin, Germany., Kim JY; Institut für Virologie, Fachbereich Veterinärmedizin, Freie Universität Berlin, Berlin, Germany., Trimpert J; Institut für Virologie, Fachbereich Veterinärmedizin, Freie Universität Berlin, Berlin, Germany.; Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Molecular biology and evolution [Mol Biol Evol] 2024 Jul 03; Vol. 41 (7). |
| DOI: | 10.1093/molbev/msae119 |
| Abstrakt: | Antiviral therapy is constantly challenged by the emergence of resistant pathogens. At the same time, experimental approaches to understand and predict resistance are limited by long periods required for evolutionary processes. Here, we present a herpes simplex virus 1 mutant with impaired proofreading capacity and consequently elevated mutation rates. Comparing this hypermutator to parental wild type virus, we study the evolution of antiviral drug resistance in vitro. We model resistance development and elucidate underlying genetic changes against three antiviral substances. Our analyzes reveal no principle difference in the evolutionary behavior of both viruses, adaptive processes are overall similar, however significantly accelerated for the hypermutator. We conclude that hypermutator viruses are useful for modeling adaptation to antiviral therapy. They offer the benefit of expedited adaptation without introducing apparent bias and can therefore serve as an accelerator to predict natural evolution. Competing Interests: Conflict of Interest The authors declare no conflict of interest. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|